Research in the laboratory is concerned with the regulation of sympathetic outflow in normal and disease states. Type 2 diabetes is one of the diseases with the greatest risk of developing cardiovascular disease. Accumulated evidence indicates that type 2 diabetes is associated with enhanced sympathetic neural drive. Chronic sympathetic activation increases the risk of cardiovascular complications and subsequent mortality during type 2 diabetes. Our central hypothesis is that enhanced leptin-glutamate signaling in the hypothalamic nuclei contributes to the exaggerated sympatho-excitation in rats with type 2 diabetes The questions are addressed using high fat and low dose streptozotocin-induced type 2 diabetic rats to define the precise mechanisms (leptin-glutamate signaling) and specialized cells (neuron-astrocyte interaction) within the hypothalamus that lead to sympatho-excitation in type 2 diabetes. Furthermore, we also study the effects of leptin through transient receptor potential canonical channels contributing to the exaggerated sympathetic activation in type 2 diabetes. The project is addressed by using whole animal study, electrophysiological study, genetic manipulation, immunohistochemistry, confocal image, neuronal cell culture and molecular biology techniques.